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PubMed2000

Emergence of item response modeling in instrument development and data analysis.

In summary, readers are encouraged to read carefully the IRT articles in this special issue. They provide theoretical as well as practical arguments in favor of using IRT models in the health outcomes measurement field. At the same time, readers should be aware that the IRT field is complex and software is limited and, in my judgment, not very user friendly (although some packages are better than others). In addition, sample sizes will often need to be larger than in classical measurement, at least with the more general IRT models, and applications are rarely straightforward. Considerable practical experience is needed to ensure successful applications of IRT in the development and validation of instruments for health outcomes measurement.

Data Interpretation, Statistical↗
PubMedDate not supplied

An analytic strategy for modeling multiple-item responses: a breast cancer symptom example.

BACKGROUND: Item Response Theory (IRT) is increasingly applied in health research to combine information from multiple-item responses. IRT posits that a person's susceptibility to a symptom is driven by the interaction of the characteristics of the symptom and person. This article describes the statistical background of incorporating IRT into a multilevel framework and extends this approach to longitudinal health outcomes, where the self-report method is used to construct a multi-item scale. METHODS: A secondary analysis of data from 2 descriptive longitudinal studies is performed. The data include 21 symptoms reported across time by 350 women with breast cancer. A 3-level hierarchical linear model (HLM) was used for the analysis. Level 1 models the item responses, consisting of symptom presence or absence. Level 2 models the trajectory of each individual, representing change over time of the IRT-created latent variable symptom experience. Level 3 explains that trajectory using person-specific characteristics such as age and location of care. The purpose of the analysis is to examine if older and younger women with breast cancer differ in their symptom experience trajectory after controlling for location of care. RESULTS: Fatigue and pain were the most prevalent symptoms. The symptom experience of women with breast cancer was found to improve over time. Neither age nor location of care was significantly associated with the symptom experience trajectory. DISCUSSION: Embedding IRT into an HLM framework produces several benefits. The example provided demonstrates benefits through the creation of a latent symptom experience variable that can be used either as an outcome or as a covariate in another model, examining the latent symptom experience trajectory and its relationship with covariates at the individual level, and managing symptom nonresponse.

Adult↗
PubMed1994

Effects of 8-OH-DPAT, 5-CT and muscimol on behaviour maintained by a DRL20 schedule of reinforcement, following microinjection into the dorsal or median raphe nuclei.

Experiments were performed to investigate the effects of microinjections of the 5-HT(1A) agonist 8- hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), the non-selective 5-HT(1) agonist 5-carboxamidotryptamine (5-CT) and the GABA(A) agonist muscimol into the midbrain raphe nuclei, on behaviour maintained by a differential reinforcement of low rate (DRL) 20 schedule of food reinforcement. Following acquisition of responding under the DRL20 schedule, in which responses were reinforced only if they occurred at least 20s after the previous response, two groups of rats were prepared with a stainless steel guide cannula aimed at either the dorsal raphe nucleus or the median raphe nucleus. Injections of 8-OH-DPAT and 5-CT into the median raphe dose-dependently increased responding and reduced the number of reinforcers earned, leading to a net reduction in response efficiency from 45% to approximately 27% (5µg 8-OH-DPAT) and 22% (375ng 5-CT). Both drugs appeared to shift the frequency distribution of inter-response times (IRTs) towards shorter IRTs, and lowered the mean IRT. These effects were not observed after dorsal raphe injections of either drug. This pattern of results, together with results obtained in other paradigms measuring response inhibition, suggests that suppression of the activity of median raphe 5-HT neurones induces deficits in the ability to withhold responding. Muscimol increased responding, decreased the number of reinforcers earned and reduced response efficiency after both dorsal raphe and median raphe injections. These effects were more pronounced following median raphe injections, and were of considerably greater magnitude than those observed following treatment with the 5-HT agonists. Muscimol injected into the median raphe lowered the mean IRT, and increased the frequency of short duration IRTs. Thus, stimulation of GABA(A) receptors within the median raphe induces a pattern of behavioural disruption in the DRL task, that is more severe than that resulting from selective inhibition of 5-HT neural activity. The effects of muscimol probably arise from a general behavioural activation, rather than a specific deficit in the ability to withhold responding.

Journal Article↗
PubMed2005

Assessment of an asthma quality of life scale using item-response theory.

OBJECTIVE: Health-related quality of life (HRQOL) scores produced by simply summing individual item values have been criticized for lacking linearity and for not being equally discriminating across the range of scores. Differences in summed scores may depend more on their starting point on the scale rather than actual differences in the underlying dimension of HRQOL, making it difficult to judge what a particular score means. We sought to examine the usefulness of an alternative method of scoring questionnaires, item-response theory (IRT), for the clinical interpretation of a modified version of the Marks Asthma Quality of Life Questionnaire (MAQLQ-M). METHODOLOGY: Using the MAQLQ-M, we surveyed 293 adults with moderate to severe asthma, managed at two university teaching hospitals in Adelaide, South Australia. Scores obtained by usual summative Likert-type scores were compared to estimates using the partial credit method of IRT. RESULTS: We found a non-linear relationship between raw, summative scores and the IRT estimates. The departure from linearity was marked for summative scores below 3.0 and above 5.0 (range 1.0-7.0), values that included half of the study patients. Summative scoring did not produce scores at the interval level of measurement. CONCLUSION: For an equivalent difference measured in the underlying dimension of actual HRQOL using IRT, traditional summated scores showed a much smaller difference in scores at both the lower and upper end of HRQOL, than at the mid-range of HRQOL. Caution should be used when interpreting HRQOL surveys scored in the usual summative manner. Advantages may be gained by using IRT as an alternative method of scoring HRQOL questionnaires.

Adolescent↗
PubMed2000

Carbohydrate supplementation attenuates muscle glycogen loss during acute bouts of resistance exercise.

The effects of carbohydrate (CHO) supplementation on muscle glycogen and resistance exercise performance were examined with eight highly resistance trained males (mean +/- SEM, age: 24.3 +/- 1.1 years, height: 171.9 +/- 2.0 cm, body mass: 85.7 +/- 3.5 kg; experience 9.9 +/- 2.0 years). Subjects participated in a randomized, double blind protocol with testing sessions separated by 7 days. Testing consisted of an initial isokinetic leg exercise before and after an isotonic resistance exercise (IRT) session consisting of 3 leg exercises lasting approximately 39 min. Subjects consumed a CHO (1.0 g CHO.kg body mass(-1)) or placebo treatment (PLC), prior to and every 10-min (0.5 g CHO.kg body mass(-1)) during the IRT. Muscle tissue was obtained from the m vastus lateralis after a supine rest (REST) immediately after the initial isokinetic test (POST-ISO) and immediately after the IRT (POST-IRT). The CHO treatment elicited significantly less muscle glycogen degradation from the POST-ISO to POST-IRT (126.9 +/- 6.5 to 109.7 +/- 7.1 mmol.kg wet weight(-1)) compared to PLC (121.4 +/- 8.1 to 88.3 +/- 6. 0 mmol.kg wet weight(-1)). There were no differences in isokinetic performance between the treatments. The results of this investigation indicate that the consumption of a CHO beverage can attenuate the decrease in muscle glycogen associated with isotonic resistance exercise but does not enhance the performance of isokinetic leg exercise.

Adult↗
PubMed2000

Epidemiological survey of amoxicillin-clavulanate resistance and corresponding molecular mechanisms in Escherichia coli isolates in France: new genetic features of bla(TEM) genes.

Amoxicillin-clavulanate resistance (MIC >16 microg/ml) and the corresponding molecular mechanisms were prospectively studied in Escherichia coli over a 3-year period (1996 to 1998) in 14 French hospitals. The overall frequency of resistant E. coli isolates remained stable at about 5% over this period. The highest frequency of resistant isolates (10 to 15%) was observed, independently of the year, among E. coli isolated from lower respiratory tract samples, and the isolation rate of resistant strains was significantly higher in surgical wards than in medical wards in 1998 (7.8 versus 2.8%). The two most frequent mechanisms of resistance for the 3 years were the hyperproduction of the chromosomal class C beta-lactamase (48, 38.4, and 39.7%) and the production of inhibitor-resistant TEM (IRT) enzymes (30.4, 37.2, and 41.2%). By using the single-strand conformational polymorphism-PCR technique and sequencing methods, we determined that 59 IRT enzymes corresponded to previously described IRT enzymes whereas 8 were new. Three of these new enzymes derived from TEM-1 by only one amino acid substitution (Ser130Gly, Arg244Gly, and Asn276Asp), whereas three others derived by two amino acid substitutions (Met69Leu and Arg244Ser, Met69Leu and Ile127Val, and Met69Val and Arg275Gln). The two remaining new IRTs showed three amino acid substitutions (Met69Val, Trp165Arg, and Asn276Asp and Met69Ile, Trp165Cys, and Arg275Gln). New genetic features were also found in bla(TEM) genes, namely, bla(TEM-1B) with either the promoters Pa and Pb, P4, or a promoter displaying a C-->G transversion at position 3 of the -35 consensus sequence and new bla(TEM) genes, notably one encoding TEM-1 but possessing the silent mutations originally described in bla(TEM-2) and then in some bla(TEM)-encoding IRT enzymes.

Amino Acid Substitution↗
PubMed2005

Quantitative assessment of regional peak myocardial acceleration during isovolumic contraction and relaxation times by tissue Doppler imaging.

OBJECTIVE: To examine regional wall acceleration and its relation to relaxation. STUDY DESIGN: 8 sheep were examined by tissue Doppler ultrasound imaging (VingMed Vivid FiVe) in apical four chamber views to evaluate the left ventricular wall divided into six segments and the mitral annulus in two segments. Peak myocardial acceleration during isovolumic periods (pIVA) derived from tissue Doppler echocardiography was analysed during isovolumic contraction (ICT) and relaxation times (IRT) in each segment. INTERVENTIONS: After scanning at baseline, haemodynamic status was changed by administration of blood, dobutamine, and metoprolol. Changes of pIVA during IRT and ICT were compared over the four haemodynamic conditions in parallel with their peak positive and negative dP/dt measured with a high frequency manometer tipped catheter. RESULTS: pIVA of the basal lateral segment during ICT correlated most strongly with peak positive dP/dt (r = 0.96, p < 0.0001) and there was good correlation between pIVA of the mitral valve annulus in the septum during IRT and peak negative dP/dt (r = 0.80, p < 0.0001). pIVA differed significantly between the four haemodynamic conditions during ICT in all segments (p < 0.05); pIVA during IRT did not differ significantly between the four conditions. CONCLUSIONS: pIVA of the basal lateral wall during ICT correlated most strongly with peak positive dP/dt, and pIVA of the septal mitral valve annulus during IRT correlated well with peak negative dP/dt.

Animals↗
PubMed1981

Serum immunoreactive trypsin in beta-thalassaemia major.

To assess the exocrine pancreatic function in beta-thalassemia major with iron overload, serum immunoreactive trypsin (IRT) was measured in 38 patients with this condition. In 23 (60%) patients' IRT was abnormal: it was subnormal in 16 patients and supranormal in seven. Whereas subnormal IRT concentrations were more frequent in patients of more than 12 years old, supranormal IRT concentrations were more frequent in younger patients. These data provide the first antemortem evidence of exocrine pancreatic damage in this condition. They also suggest that this acinar cell damage is initially associated with a rise in IRT which is followed by a fall in the serum concentration of this enzyme.

Adolescent↗
PubMed1982

Comparison of the diagnostic value of serum pancreatic isoamylase and immunoreactive trypsin measurement in patients with cystic fibrosis.

We have measured serum immunoreactive trypsin (IRT) and serum pancreatic isoamylase (PIA) activities using commercially available kits in 37 cystic fibrosis (CF) patients and 46 hospital controls of similar age range. Immunoreactive trypsin was more often abnormal than PIA (26/37 v 18/37 abnormal respectively); IRT will be particularly useful as an additional diagnostic test in older children, in whom interpretation of the sweat test may be difficult, as 14/15 CF patients aged over 10 years had abnormal IRT results. Less than half of our patients who were aged between one and nine years had abnormal IRT activity, limiting the value of the test, though a low activity would still support the diagnosis of CF. Comparison with faecal fat estimations in 31 patients suggests that neither IRT nor PIA can be used as a non-invasive test of pancreatic function in order to identify those few CF patients who do not require pancreatic enzyme supplements.

Adolescent↗
PubMed1997

CFTR mutations and IVS8-5T variant in newborns with hypertrypsinaemia and normal sweat test.

Neonates positive for immunoreactive trypsinogen assay (IRT) and negative for sweat test have formerly been found to carry the major cystic fibrosis (CF) mutation, delta F508, much more frequently than the general population. Among the 716 IRT positive newborns detected by a three tier (IRT, mutation analysis plus meconium lactase assay, sweat test) CF screening programme in north eastern Italy during the period January 1993 to March 1996, we found 45 carriers, a number significantly higher than the expected 17 (p < 0.001). We speculated that some of these heterozygotes could actually be affected by a very mild form of CF, and carry on the other chromosome an undetected CFTR mutation or a DNA variant, such as the 5-thymidine allele in intron 8 of the CFTR gene (IVS8-5T). This hypothesis was tested in four samples; group A (the 45 carriers mentioned above), group B (51 non-carrier, IRT positive neonates), group C (50 IRT negative neonates), and group D (90 CF adult female carriers). Chromosomes with IVS8-5T were seven (7.78%) in group A, seven (6.86%) in group B, five (5%) in group C, and four in group D (2.22%). The 5T prevalence in group A was significantly higher (p < 0.05) compared to group D; similarly, a higher (p < 0.05) 5T frequency in group A compared to group C was detected by considering the chromosomes free from CFTR mutations. This study is consistent with previous papers in finding among neonates with high trypsin levels a CF carrier frequency significantly higher than that expected. It is also suggested that in at least some babies raised trypsin levels at birth could be a phenotypic expression of compound heterozygosity for a major CF mutation plus IVS8-5T.

Adult↗
PubMed1980

Plasma-immunoreactive trypsin in chronic renal failure.

Plasma-immunoreactive trypsin (IRT) was measured by radioimmunoassay in 52 patients with chronic renal failure. 29 were on conservative treatment, 14 on-regular haemodialysis, and 9 on regular haemofiltration. IRT levels were elevated in those with raised plasma creatinine and there was a significant positive correlation to plasma creatinine concentrations (r = 0.853; p less than 0.001). IRT levels were not significantly altered by haemodialysis or haemofiltration. It is concluded that the kidney plays an important role in the metabolism of plasma trypsin. Since plasma IRT levels may be elevated in patients with chronic renal failure, the IRT determination may be misleading in diagnosing acute and chronic pancreatitis in the presence of kidney disease.

Creatinine↗
PubMed2005

Item response theory and its applications to patient-reported outcomes measurement.

This article provides an overview of item response theory (IRT) models and how they can be appropriately applied to patient-reported outcomes (PROs) measurement. Specifically, the following topics are discussed: (a) basics of IRT, (b) types of IRT models, (c) how IRT models have been applied to date, and (d) new directions in applying IRT to PRO measurements.

Health Services Research↗
PubMed2004

Population-based newborn screening for genetic disorders when multiple mutation DNA testing is incorporated: a cystic fibrosis newborn screening model demonstrating increased sensitivity but more carrier detections.

OBJECTIVES: Newborn screening for cystic fibrosis (CF) provides a model to investigate the implications of applying multiple-mutation DNA testing in screening for any disorder in a pediatric population-based setting, where detection of affected infants is desired and identification of unaffected carriers is not. Widely applied 2-tiered CF newborn screening strategies first test for elevated immunoreactive trypsinogen (IRT) with subsequent analysis for a single CFTR mutation (DeltaF508), systematically missing CF-affected infants with any of the >1000 less common or population-specific mutations. Comparison of CF newborn screening algorithms that incorporate single- and multiple-mutation testing may offer insights into strategies that maximize the public health value of screening for CF and other genetic disorders. The objective of this study was to evaluate technical feasibility and practical implications of 2-tiered CF newborn screening that uses testing for multiple mutations (multiple-CFTR-mutation testing). METHODS: We implemented statewide CF newborn screening using a 2-tiered algorithm: all specimens were assayed for IRT; those with elevated IRT then had multiple-CFTR-mutation testing. Infants who screened positive by detection of 1 or 2 mutations or extremely elevated IRT (>99.8%; failsafe protocol) were then referred for definitive diagnosis by sweat testing. We compared the number of sweat-test referrals using single- with multiple-CFTR-mutation testing. Initial physician assessments and diagnostic outcomes of these screened-positive infants and any affected infants missed by the screen were analyzed. We evaluated compliance with our screening and follow-up protocols. All Massachusetts delivery units, the Newborn Screening Program, pediatric health care providers who evaluate and refer screened-positive infants, and the 5 Massachusetts CF Centers and their affiliated genetic services participated. A 4-year cohort of 323 506 infants who were born in Massachusetts between February 1, 1999, and February 1, 2003, and screened for CF at approximately 2 days of age was studied. RESULTS: A total of 110 of 112 CF-affected infants screened (negative predictive value: 99.99%) were detected with IRT/multiple-CFTR-mutation screening; 2 false-negative screens did not show elevated IRT. A total of 107 (97%) of the 110 had 1 or 2 mutations detected by the multiple- CFTR-mutation screen, and 3 had positive screens on the basis of the failsafe protocol. In contrast, had we used single-mutation testing, only 96 (87%) of the 110 would have had 1 or 2 mutations detectable by single-mutation screen, 8 would have had positive screens on the basis of the failsafe protocol, and an additional 6 infants would have had false-negative screens. Among 110 CF-affected screened-positive infants, a likely "genetic diagnosis" was made by the multiple-CFTR-mutation screen in 82 (75%) versus 55 (50%) with DeltaF508 alone. Increased sensitivity from multiple-CFTR-mutation testing yielded 274 (26%) more referrals for sweat testing and carrier identifications than testing with DeltaF508 alone. CONCLUSIONS: Use of multiple-CFTR-mutation testing improved sensitivity and postscreening prediction of CF at the cost of increased referrals and carrier identification.

Algorithms↗
PubMed1963

The effects of drl schedules on some characteristics of word utterance.

The utterances of particular words-"selected verbal responses" (SVR's)-were reinforced according to five different drl schedules and studied under changes in the schedule and/or the SVR. The emissions of SVR's were shaped by the procedure, while the rates of saying all the different words were unaffected. The distributions of the percentages of different IRT's and IRT's/OP's changed very little when only the SVR was changed, suggesting that reinforcements had their main effect upon some kind of "delaying behavior." The modal IRT classes were just above the drl specifications, and there was no evidence of a second modal class at short IRT's. The differences between actual and optimum median IRT's were fairly constant under different drl schedules. Individual differences appeared in the behavior interpolated between SVR's: some subjects (Ss) counted the number of intervening words, some reported increases in tension, and still others seemed to change the pitch of voice in a cyclical pattern. The transcripts of intervening verbal behavior indicated the presence of some chains of words, presumably formed before the experiment and "adapted" to the length of the delay required for reinforcement. In the experimental situation the formation of verbal chains was only rarely observable.

Learning↗
PubMed1967

Response patterning during stimulus generalization in the rat.

Nine rats were trained to bar press in the presence of a clicking sound of 6.67 cps (S(D)) for 1-min variable-interval food reinforcement randomly alternated with a clicking sound of 20 cps (S(Delta)) signifying extinction. After a criterion of 90% of total responses in the presence of the S(D) was obtained, a generalization test was administered, including values of 6.67, 10.00, 13.33, and 20.00 cps, with responses in the presence of the S(D) continuing to be reinforced during testing. The test yielded a gradient of response strength with rate highest in the presence of the S(D) and decreasing with increasing distance from this value. An interresponse time (IRT) analysis of responding during generalization testing revealed no systematic differences in modal IRT category or in median IRT to the different test stimuli. Mean IRT was lowest in the presence of the S(D) and increased systematically with increasing distance from this value, supporting the hypothesis that the generalization gradient of response rate is primarily the result of an increasing proportion of "long" IRT responses to stimuli increasingly distant from the S(D).

Animals↗
PubMed1968

The distribution of interresponse times in the pigeon during variable-interval reinforcement.

Three pigeons' pecks were reinforced on 1- and 2-min variable-interval schedules, and frequency distributions of their interresponse times (IRTs) were recorded. The conditional probability that a response would fall into any IRT category was estimated by the interresponse-times-per-opportunity transformation (IRTs/op). The resulting functions were notable chiefly for the relatively low probability of IRTs in the 0.2- to 0.3-sec range; in other respects they varied within and between subjects. The overall level of the curves generally rose over the course of 32 experimental hours, but their shapes changed unsystematically. The shape of the IRT distribution was much the same for VI 1-min and VI 2-min. The variability of these distributions supports the notion that the VI schedule only loosely controls response rate, permitting wide latitude to adventitious effects. There was no systematic evidence that curves changed over sessions to conform to the distribution of reinforcements by IRT.

Animals↗
PubMed1985

Discriminated interresponse times: role of autoshaped responses.

When discriminated interresponse-time (IRT) procedures have been used to assess preference relations among temporally extended operants, deviations from matching have been obtained. Using a yoked-control procedure, the present study found that key pecking in a discriminated IRT procedure has two sources of strength--that arising from the response-reinforcer contingency that is explicitly arranged, and that arising from a stimulus-reinforcer contingency that is a by-product of the explicitly arranged contingency. The key pecking of all lead birds, and that of 3 of the 4 birds exposed to a yoked autoshaping procedure, was controlled by the keylight that signaled the lead birds' criterion IRTs. Because stimulus control of key pecking by the keylight, whether autoshaped or discriminative, fosters deviations from matching, the discriminated IRT procedure does not provide an appropriate basis for conclusions about preference relations among IRTs.

Animals↗
PubMed1987

Amniotic immunoreactive trypsin in pregnancies with normal and pathological outcomes.

Immunoreactive trypsin (IRT) has been studied in amniotic fluid as a possible complementary test substance for the prenatal diagnosis of cystic fibrosis (CF). 219 normal amniotic fluids have been tested in order to establish the normal ranges from 14 to 40 gestational weeks (g.w.). The IRT level increases from g.w. 14 to 19, remains stable from g.w. 19 to 25 and then decreases rapidly to low levels. A retrospective study of 4 presumed CF fluids, as determined by abnormal alkaline phosphatase levels, showed decreased IRT values in 3 out of 4 fluids. The difference between the mean value and the normal mean was not significant. The prospective study allowed us to test 2 fluids from pregnancies affected by meconium ileus. IRT level was highly elevated, 530 times the normal mean value at g.w. 34 for a non-CF fetus and 18 times the normal mean value for a CF fetus at g.w. 31. In 4 out of 5 cases of fetal severe intra-uterine growth retardation, IRT levels appeared mildly elevated. Other abnormalities are reviewed.

Amniotic Fluid↗